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Differential Patterns of IgG Subclass Responses to Plasmodium falciparum Antigens in Relation to Malaria Protection and RTS,S Vaccination

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  • Carlota Dobaño
  • Rebeca Santano
  • Marta Vidal
  • Alfons Jiménez
  • Chenjerai Jairoce
  • Itziar Ubillos
  • David Dosoo
  • Ruth Aguilar
  • Nana Aba Williams
  • Núria Díez-Padrisa
  • Aintzane Ayestaran
  • Clarissa Valim
  • Kwaku Poku Asante
  • Seth Owusu-Agyei
  • David Lanar
  • Virander Chauhan
  • Chetan Chitnis
  • Sheetij Dutta
  • Evelina Angov
  • Benoit Gamain
  • Ross L. Coppel
  • James G. Beeson
  • Linda Reiling
  • Deepak Gaur
  • Ben Gyan
  • Augusto J. Nhabomba
  • Joseph J. Campo
  • Gemma Moncunill

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    Rights statement: Copyright © 2019 Dobaño, Santano, Vidal, Jiménez, Jairoce, Ubillos, Dosoo, Aguilar, Williams, Díez-Padrisa, Ayestaran, Valim, Asante, Owusu-Agyei, Lanar, Chauhan, Chitnis, Dutta, Angov, Gamain, Coppel, Beeson, Reiling, Gaur, Cavanagh, Gyan, Nhabomba, Campo and Moncunill. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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    Licence: Creative Commons: Attribution (CC-BY)

Original languageEnglish
Article number439
Pages (from-to)1-19
Number of pages19
JournalFrontiers in Immunology
Volume10
DOIs
StatePublished - 15 Mar 2019

Abstract

Naturally acquired immunity (NAI) to Plasmodium falciparum malaria is mainly mediated by IgG antibodies but the subclasses, epitope targets and effector functions have not been unequivocally defined. Dissecting the type and specificity of antibody responses mediating NAI is a key step toward developing more effective vaccines to control the disease. We investigated the role of IgG subclasses to malaria antigens in protection against disease and the factors that affect their levels, including vaccination with RTS,S/AS01E. We analyzed plasma and serum samples at baseline and 1 month after primary vaccination with RTS,S or comparator in African children and infants participating in a phase 3 trial in two sites of different malaria transmission intensity: Kintampo in Ghana and Manhiça in Mozambique. We used quantitative suspension array technology (qSAT) to measure IgG1−4 responses to 35 P. falciparum pre-erythrocytic and blood stage antigens. Our results show that the pattern of IgG response is predominantly IgG1 or IgG3, with lower levels of IgG2 and IgG4. Age, site and RTS,S vaccination significantly affected antibody subclass levels to different antigens and susceptibility to clinical malaria. Univariable and multivariable analysis showed associations with protection mainly for cytophilic IgG3 levels to selected antigens, followed by IgG1 levels and, unexpectedly, also with IgG4 levels, mainly to antigens that increased upon RTS,S vaccination such as MSP5 and MSP1 block 2, among others. In contrast, IgG2 was associated with malaria risk. Stratified analysis in RTS,S vaccinees pointed to novel associations of IgG4 responses with immunity mainly involving pre-erythrocytic antigens upon RTS,S vaccination. Multi-marker analysis revealed a significant contribution of IgG3 responses to malaria protection and IgG2 responses to malaria risk. We propose that the pattern of cytophilic and non-cytophilic IgG antibodies is antigen-dependent and more complex than initially thought, and that mechanisms of both types of subclasses could be involved in protection. Our data also suggests that RTS,S efficacy is significantly affected by NAI, and indicates that RTS,S vaccination significantly alters NAI.

    Research areas

  • IgG subclass, Malaria, Plasmodium falciparum, antibody, children, naturally acquired immunity, protection, vaccine

ID: 81824423